Brain Research[JOURNAL]
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200 papers
Vestibular brainstem impairment following in utero exposure to high dose paracetamol.
Graeca M, Donnelly A, Cain L … +1 more , Kulesza R
Brain Res · 2026 Jul · PMID 41881273 · Publisher ↗
Paracetamol (PAR) is an analgesic and antipyretic medication and is regarded as the safest over-the-counter option for relief of pain and fever during pregnancy. Importantly, PAR and its metabolites can reach the fetus t...
Paracetamol (PAR) is an analgesic and antipyretic medication and is regarded as the safest over-the-counter option for relief of pain and fever during pregnancy. Importantly, PAR and its metabolites can reach the fetus through direct placental transfer and subsequently cross the fetal blood brain barrier. While the use of PAR at therapeutic levels during pregnancy is advised to impart no increased risk of neurodevelopmental impairment, in utero exposure to high dose (HD) PAR does result in neurological dysfunction in both human subjects and animal models. To explore the impact of HD in utero PAR exposure on brainstem function, we examined click-evoked auditory brainstem responses (ABR) and found that PAR-exposed animals had delayed ear opening, elevated thresholds, and significant delays in ABR waves I-V, implicating widespread brainstem dysfunction. Since auditory and vestibular dysfunction commonly occur together in neurodevelopmental conditions, we hypothesized that in utero exposure to HD PAR would also result in vestibular impairment. We investigated this hypothesis using a battery of sensorimotor tasks, cervical vestibular-evoked myogenic potentials (cVEMPs) and quantitative morphometrics. PAR-exposed animals had significantly worse performance on sensorimotor tasks, delayed cVEMPs and significantly fewer neurons in the vestibular nuclei. Together, our findings indicate that in utero exposure to HD PAR results in significant functional and structural changes in the vestibular brainstem and suggest that vestibular assessments may be used to screen newborns for congenital brainstem impairments.
YTHDF1 promotes neuronal pyroptosis in cerebral ischemia/reperfusion injury by m6A-dependent stabilization of NEK7.
Wang X, Wang L
Brain Res · 2026 Jul · PMID 41865965 · Publisher ↗
Pyroptosis is a pathological process contributing to cerebral ischemia/reperfusion (I/R) injury. YTHDF1 participates in various pathological mechanisms including pyroptosis; however, its regulatory role in pyroptosis dur...
Pyroptosis is a pathological process contributing to cerebral ischemia/reperfusion (I/R) injury. YTHDF1 participates in various pathological mechanisms including pyroptosis; however, its regulatory role in pyroptosis during cerebral I/R injury remains poorly understood. This study aimed to investigate the functional role and underlying molecular mechanisms of YTHDF1 in cerebral I/R injury with a focus on neuronal pyroptosis. I/R-induced rat models and oxygen-glucose deprivation and reoxygenation (OGD/R)-induced neuronal cell models were established. Infarct areas were visualized using TTC staining. Cellular viability, oxidative stress levels, and pyroptotic activity were evaluated through gain- and loss-of-function experiments. The regulatory relationship between YTHDF1 and NEK7 was analyzed using RNA immunoprecipitation, dual-luciferase reporter assays, and RNA stability detection. Our results demonstrated that YTHDF1 expression was significantly upregulated in both I/R rat models and OGD/R-treated cells. YTHDF1 knockdown suppressed pyroptotic processes while enhancing antioxidant capacity. Furthermore, YTHDF1 physically interacted with NEK7, specifically binding to the m6A modification site within Nek7 mRNA to maintain its RNA stability. NEK7 overexpression effectively counteracted the anti-pyroptotic effects induced by YTHDF1 silencing. In vivo experiments confirmed that YTHDF1 inhibition reduced infarct volume and attenuated pyroptosis in cerebral I/R injury via decreasing NEK7 expression. These findings demonstrate that YTHDF1 promotes neuronal pyroptosis by stabilizing NEK7, thereby exacerbating cerebral I/R injury, suggesting its potential as a therapeutic target for ischemic stroke treatment.
Editorial: Challenging our understanding of neurological and neuropsychiatric disorders by means of hybrid biological and technological tools: novel approaches in computational neuroscience, neuroengineering, and artificial intelligence.
Cota VR, Garcia-Cairasco N
Brain Res · 2026 Jun · PMID 41864257 · Publisher ↗
Abstract loading — click title to view on PubMed.
Dopaminergic neurons in the dorsal raphe nucleus are involved in the regulation of memory impairment in chronic pain.
Wang L, Wang G, Zhao W … +6 more , Meng X, Xie C, Sun H, Zhang Y, Kang P, Ji F
Brain Res · 2026 Jul · PMID 41864256 · Publisher ↗
BACKGROUND: Chronic pain is a prevalent condition often associated with cognitive impairments, including memory deficits. The dorsal raphe nucleus (DRN) is implicated in both pain processing and memory regulation, yet th...
BACKGROUND: Chronic pain is a prevalent condition often associated with cognitive impairments, including memory deficits. The dorsal raphe nucleus (DRN) is implicated in both pain processing and memory regulation, yet the role of DRN dopaminergic (DAergic) neurons in chronic pain-induced memory impairment remains unclear. This study aimed to investigate whether DRN-DA neurons and their projections to the bed nucleus of the stria terminalis (BNST) contribute to memory deficits in a mouse model of chronic neuropathic pain. METHODS: Chronic constrictive injury (CCI) was induced in male C57BL/6J and DAT-Cre mice to establish neuropathic pain. Memory function was assessed using the novel object recognition (NOR) and fear conditioning tests (FCT). Neuronal activity was evaluated via c-Fos immunohistochemistry and whole-cell patch-clamp recordings. Chemogenetic and optogenetic techniques were employed to selectively manipulate DRN-DA neurons and their projections to the BNST. RESULTS: CCI mice exhibited significant memory impairments alongside reduced activity of DRN-DA neurons. Chemogenetic or optogenetic activation of DRN-DA neurons alleviated memory deficits in CCI mice. Optogenetic stimulation of DRN-DA terminals in the BNST similarly rescued memory performance, confirming the involvement of the DRN-BNST pathway in pain-related cognitive dysfunction. CONCLUSION: Our findings demonstrate that DRN-DA neurons play a critical role in regulating memory impairment induced by chronic pain, partly through projections to the BNST. Targeted activation of this pathway may represent a potential therapeutic strategy for alleviating cognitive deficits in chronic pain conditions.
Advancing brain health research through an integrative framework.
Brain Res · 2026 Jun · PMID 41864255 · Publisher ↗
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Construction of ammonia death-related lncRNA prognostic signature model and immunomodulatory effect in glioblastoma multiforme.
Han Z, Zhong C, Tan E … +2 more , He M, Liu J
Brain Res · 2026 Jul · PMID 41861940 · Publisher ↗
BACKGROUND: Glioblastoma (GBM) is characterized by "glutamine addiction," a metabolic state that generates toxic ammonia byproducts. We explored the prognostic value of long non-coding RNAs (lncRNAs) associated with ammo...
BACKGROUND: Glioblastoma (GBM) is characterized by "glutamine addiction," a metabolic state that generates toxic ammonia byproducts. We explored the prognostic value of long non-coding RNAs (lncRNAs) associated with ammonia-induced cell death-a novel mechanism distinct from apoptosis and ferroptosis-to identify potential biomarkers and elucidate the metabolic-immune landscape of GBM. METHODS: Ammonia death-associated genes were identified via co-expression analysis in TCGA-GBM datasets. A prognostic signature was constructed using LASSO-Cox regression and validated in independent CGGA cohorts. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize cellular heterogeneity and map ammonia death scores to specific cell populations. The expression of signature lncRNAs was validated in vitro using human GBM cell lines (U-251, U-87 MG) and normal human astrocytes via RT-qPCR. RESULTS: A robust three-lncRNA signature (LINC00645, AC011451.4, AC093627.22) was established. The high-risk score served as an independent predictor of significantly poorer overall survival (P < 0.001). scRNA-seq revealed that regulatory T cells (Tregs) and macrophages exhibited the highest ammonia death scores. Consistently, high-risk tumors displayed a profoundly immunosuppressive microenvironment, characterized by increased infiltration of M2 macrophages and Tregs, elevated ESTIMATE scores, and upregulation of immune checkpoints (e.g., PD-L1, IDO1). RT-qPCR results confirmed the dysregulated expression of these lncRNAs in GBM cells consistent with bioinformatic predictions. CONCLUSIONS: This novel signature effectively links metabolic ammonia stress to immune evasion in GBM. It serves as a reliable prognostic tool and suggests that targeting the ammonia death-related metabolic-immune axis could offer new avenues for personalizing immunotherapy.
Nuclear distribution element 1 is involved in cell proliferation in the ventricular-subventricular zone during early postnatal brain development.
Shimizu S, Ishino Y, Miyata S
Brain Res · 2026 Jul · PMID 41861939 · Publisher ↗
The ventricular-subventricular zone (V-SVZ) is a specialized neurogenic niche localized on the walls of the lateral ventricles in the postnatal mammalian brain. In the V-SVZ, neural stem cells (NSCs) generate transit-amp...
The ventricular-subventricular zone (V-SVZ) is a specialized neurogenic niche localized on the walls of the lateral ventricles in the postnatal mammalian brain. In the V-SVZ, neural stem cells (NSCs) generate transit-amplifying neural progenitor cells, which produce neuroblasts. V-SVZ-derived neuroblasts have proliferative potential and migrate through the rostral migratory stream (RMS) toward the olfactory bulb (OB), where they differentiate into OB interneurons. However, the manner in which V-SVZ cell proliferation and OB neurogenesis are regulated during early postnatal brain development, a transition period from embryonic to adult stage, remains unclear. We focused on the role of the dynein cofactor nuclear distribution element 1 (NDE1) in early postnatal brain development. We found that Nde1 mRNA is expressed in NSCs, transit-amplifying neural progenitor cells, and neuroblasts in the V-SVZ in mice at early postnatal stage, and this expression was detected in migrating neuroblasts in the RMS and OB. Nde1 knockdown via the in vivo postnatal electroporation of Nde1 short hairpin RNA (shRNA) in a neonatal mouse brain decreased V-SVZ cell proliferation, which was rescued by overexpression of wild-type NDE1-shRNA resistant but not by overexpression of dynein-binding region-deficient NDE1-shRNA resistant. The V-SVZ cell proliferation defect was followed by impaired proliferation of V-SVZ-derived neuroblasts, thus leading to decreased generation of neuroblasts, which resulted in the reduction of newly generated OB neurons. Therefore, these results indicate that NDE1 is involved in the proliferation of NSCs and neural progenitors in the developing V-SVZ, suggesting that NDE1 plays an important role in early postnatal V-SVZ-derived neurogenesis.
HS protects hippocampal HT22 neurons against rotenone-induced ferroptosis by upregulating Isthmin 1.
Shuai XY, Du L, Wei HJ … +3 more , Zhang P, Zou W, Tang XQ
Brain Res · 2026 Jun · PMID 41846040 · Publisher ↗
BACKGROUND: Hydrogen sulfide (HS) has been recognized for its potent neuroprotective effects in Parkinson's disease (PD) models, yet the underlying cellular and molecular mechanisms remain to be fully elucidated. Ferropt...
BACKGROUND: Hydrogen sulfide (HS) has been recognized for its potent neuroprotective effects in Parkinson's disease (PD) models, yet the underlying cellular and molecular mechanisms remain to be fully elucidated. Ferroptosis, an iron-dependent form of regulated cell death, is increasingly implicated in the pathogenesis of PD. Isthmin 1 (ISM1) is a secreted protein predominantly expressed in the brain with emerging roles in neuroprotection and metabolic regulation. This study aimed to investigate whether HS protects against rotenone (ROT)-induced neuronal injury by modulating ferroptosis and to explore the potential mediating role of ISM1 in this process. METHODS: HT22 cells were exposed to ROT with or without the HS donor NaHS. Cell viability was assessed using the CCK-8 assay, and morphology was evaluated by transmission electron microscopy (TEM). Intracellular Fe was measured using the Ferrous Ion Content Assay Kit. Malondialdehyde (MDA) and glutathione (GSH) were measured using ELISA Kits. The production of cytosolic and lipid reactive oxygen species (ROS) was measured using Flow cytometry. Protein levels of Glutathione Peroxidase 4 (GPX4), Ferritin Heavy Polypeptide 1 (FTH1), and Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4) were analyzed by Western blot. RESULTS: NaHS markedly attenuated ROT-induced ferroptosis in HT22 cells. This was confirmed by suppression of mitochondrial injury, reduction in Fe accumulation and lipid peroxidation, upregulation of the ferroptosis-related proteins GPX4 and FTH1, and downregulation of ACSL4. NaHS also increased ISM1 expression. Importantly, overexpression of ISM1 was sufficient to inhibit ROT-induced ferroptosis and lipid peroxidation. CONCLUSION: These results indicate that HS counteracts ROT-induced ferroptosis in hippocampal neurons, at least in part, by upregulating ISM1, revealing a novel HS-ISM1-ferroptosis axis in neuroprotection.
Mechanisms of glymphatic system dysfunction in central nervous system diseases.
Ouyang Q, Luo L, Li J … +2 more , Chen Z, Xu Y
Brain Res · 2026 Jun · PMID 41839326 · Publisher ↗
In recent years, with the continuous development of scientific and technological means, human understanding of previously unknown or insufficiently recognized physiological structures is gradually being decrypted, and th...
In recent years, with the continuous development of scientific and technological means, human understanding of previously unknown or insufficiently recognized physiological structures is gradually being decrypted, and the exploration of the causes of disease occurrence and development has become more thorough. As a newly discovered intracranial material transport system, the glymphatic system is named after its similarity to the lymphatic circulatory system. Its structure and function are gradually being understood, and its mechanism of action in central nervous system diseases is constantly being explored. More and more studies have confirmed the important relationship between glymphatic system dysfunction and central nervous system diseases from human, animal, and cell dimensions, and more and more evidence has revealed that regulating glymphatic system function is helpful to treat central nervous system diseases from behavior, imaging, pathology, and molecule. Therefore, this paper will review the glymphatic system from three aspects: structure, function, and mechanism in central nervous system diseases, with the intention of elaborating the mechanism of glymphatic system dysfunction in central nervous system diseases, and then contributing to its further research and exploration.
Prenatal stress history modifies adolescent stress effects on adult social behavior and basolateral amygdala GABAergic neurons with perineuronal nets.
Chavez MC, Tremblay JT, Zajkowski M … +6 more , Ragusa M, Jones MM, Whaley AR, Pounders TM, Lau BY, Schulz KM
Brain Res · 2026 Jul · PMID 41839325 · Full text
Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the a...
Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the amygdala, are disrupted by stress and implicated in stress-related psychopathologies. Using a rodent model, the current study investigated the isolated and combined effects of prenatal and adolescent stress on adult social interactions and GABAergic neurons surrounded by perineuronal nets (PNNs) in the basolateral amygdala (BLA). Male and female rats were exposed to chronic variable stressors (CVS) prenatally (PS), during adolescence (AS), or during both prenatal and adolescent periods (PS + AS). In adulthood, all animals were tested for social behavior with same-sex weight-matched partners, and brains were collected for identification of BLA inhibitory neurons (GAD67 staining) and PNNs (Wisteria Floribunda Agglutinin staining). Significant prenatal × adolescent stress interactions were observed for both social behavior and BLA inhibitory neuron measures. For social behavior, AS alone increased social investigation in adulthood relative to non-stressed (NS) controls and animals exposed to combined PS + AS. PS + AS subjects did not significantly differ from NS controls, suggesting that prenatal stress exposure prevented adolescent stress-induced increases in adult social investigation. An analogous data pattern was observed in the BLA. AS alone significantly decreased the number of GAD67 + neurons surrounded by PNNs (co-labeled) relative to NS controls and showed a trend toward a decrease relative to combined PS + AS (p = 0.07). The number of co-labeled cells did not differ between combined PS + AS and NS controls. Assessment of the percentage of total GAD67 + neurons co-labeled with PNNs revealed that PS alone reduced the proportion of GAD67 + neurons surrounded by PNNs, while AS alone showed a trend toward reduction (p = 0.06). Combined PS + AS did not alter this measure relative to NS controls. Overall, these findings support a developmental interaction model in which prenatal stress alters the impact of adolescent stress on both BLA inhibitory neuron-associated perineuronal nets and adult social behavior.
Sodium fluoride exposure induced cognitive impairment via disorders synaptic protein expression and neuronal development in mice brain.
Chen L, Wang R, Jia P … +6 more , Jiang Q, An S, Yin Z, Hu D, Ning H, Ge Y
Brain Res · 2026 Jun · PMID 41833927 · Publisher ↗
As an environmental pollutant, fluoride is widespread in the natural environment in different forms, and drinking water is the primary way of exposure in human and animals. Structural damage to the central nervous system...
As an environmental pollutant, fluoride is widespread in the natural environment in different forms, and drinking water is the primary way of exposure in human and animals. Structural damage to the central nervous system may occur in human and animals after fluoride exposure, which can lead to cognitive dysfunction. However, the mechanism of cognitive impairment caused by fluoride remains unclear. In this research, a fluoride-exposed model of mice and HT-22 cells was established to explore the neurotoxic mechanisms of fluoride. In vitro, CCK-8 results showed that HT-22 cells decreased with the increase in fluoride concentrations, and the morphology appeared abnormal. Similarly, laser confocal microscopy revealed that the number of axons and dendrites decreased with the increase in fluoride concentrations. Western blot results showed that the expression level of synaptic and cytoskeleton-associated proteins decreased in fluoride groups. In vivo, the mice exhibited losses in body and brain weights in the fluoride groups compared with the control group. The step-down test demonstrated that the cognitive ability of mice in the fluoride groups significantly decreased compared with that in the control group. Western blot results showed that the expression of synaptic and cytoskeleton-associated proteins decreased in the low-fluoride group compared with the control group, and qRT-PCR results showed that PSD95 expression decreased significantly compared with the control group. These results indicated that cognitive impairment induced by fluoride is involved in the morphological damage of synapse and the abnormal expression of synaptic proteins.
Retraction notice to "Sulforaphane protects brains against hypoxic-ischemic injury through induction of Nrf2-dependent phase 2 enzyme" [Brain Res. 1343 (2010) 178-185].
Ping Z, Liu W, Kang Z … +7 more , Cai J, Wang Q, Cheng N, Wang S, Wang S, Zhang JH, Sun X
Brain Res · 2026 May · PMID 41832095 · Publisher ↗
Abstract loading — click title to view on PubMed.
Ding-zhi-xiao-wan attenuates Alzheimer's disease pathology and cognitive deficits in mouse model.
Miao Z, Yang Z, Huang Q … +5 more , Fan J, Sun J, Wang L, Zheng Y, Yang G
Brain Res · 2026 Jun · PMID 41825647 · Publisher ↗
BACKGROUND: Ding-zhi-xiao-wan (DZXW) is a classic prescription applied for the therapy of forgetfulness and dizziness. However, the mechanisms of DZXW in ameliorating cognition deficits in Alzheimer's disease (AD) have n...
BACKGROUND: Ding-zhi-xiao-wan (DZXW) is a classic prescription applied for the therapy of forgetfulness and dizziness. However, the mechanisms of DZXW in ameliorating cognition deficits in Alzheimer's disease (AD) have not been fully determined. To comprehensively illuminate the overall beneficial effects and the underlying molecular mechanisms of DZXW to AD. METHODS: An initial network pharmacology analysis was performed, including of construction of multiple networks and enrichment of gene ontology, and analysis of signal pathway. Furthermore, animal experiments were performed to validate the predicted molecular mechanisms from network pharmacology. RESULTS: 39 active compounds in DZXW corresponding to 224 genes related to AD protection were found. The therapeutic mechanisms of DZXW to protect AD predicted from the network pharmacology were primarily related to the negative regulation of neuroinflammation and oxidative stress. Compared to AD model mice, DZXW-administeredmice explored new objects more often, demonstrated a significantly shorter escape latency, passed through the platform more frequently, and stayed in the platform quadrant longer. Furthermore, DZXW-administeredmice showed a markedly less burden of Aβ plaques, lower number of activated microglias in the mice brain, enhanced activity of superoxide dismutase (SOD) and glutathione (GSH), and lower level of malondialdehyde (MDA) in mice. CONCLUSIONS: DZXW could be a therapeutic candidate for AD by inhibiting neuroinflammation and oxidative stress.
Exploring the role of glial cells and inflammatory cytokines in chronic muscle pain from rodent models.
Freitas MF, Ribeiro MP, Grande MC … +2 more , Marques NF, Chacur M
Brain Res · 2026 Jun · PMID 41819519 · Publisher ↗
Musculoskeletal disorders are among the leading causes of disability worldwide, yet their underlying mechanisms remain incompletely understood. Experimental models of gastrocnemius muscle injury have been widely used to...
Musculoskeletal disorders are among the leading causes of disability worldwide, yet their underlying mechanisms remain incompletely understood. Experimental models of gastrocnemius muscle injury have been widely used to investigate the pathophysiology of chronic muscle pain. This study aimed to evaluate histological alterations in muscle tissue, nociceptive sensitivity, locomotor activity, and the role of spinal glial cells and inflammatory mediators following the induction of chronic myositis. Histological analyses revealed marked inflammation in the muscle tissue of myositis animals. Behavioral testing confirmed pain development, with reduced nociceptive thresholds compared to controls, as well as impaired locomotor activity. Increased expression of microglia in the lumbar spinal cord was also observed in myositis animals. Importantly, pharmacological inhibition of microglial activity using minocycline significantly improved nociceptive outcomes, reinforcing the potential of glial modulation in pain control. At the systemic level, cytokine analysis showed elevated levels of the anti-inflammatory cytokines IL-4 and IL-10, accompanied by reduced fractalkine and TNF-α levels in serum, suggesting activation of compensatory mechanisms that counterbalance the inflammatory process. Collectively, these findings advance our understanding of the cellular and molecular pathways involved in chronic muscle pain. By highlighting the contribution of glial cells and specific cytokines, our results support novel therapeutic approaches aimed at modulating neuroimmune interactions.
Sex-and age- dependent modulation of synaptic proteins and behavioral variability in a postnatal valproic acid model.
Tughan E, Dana H, Yilmaz ON … +4 more , Kocum F, Demiruz C, Demirci E, Sener EF
Brain Res · 2026 Jul · PMID 41819518 · Publisher ↗
Valproic acid (VPA) exposure is widely used to model autism spectrum disorder (ASD)-like phenotypes; however, the developmental timing and sex-specific molecular consequences of postnatal exposure remain incompletely und...
Valproic acid (VPA) exposure is widely used to model autism spectrum disorder (ASD)-like phenotypes; however, the developmental timing and sex-specific molecular consequences of postnatal exposure remain incompletely understood. Disruptions in synaptogenesis and synaptic protein dynamics are considered central to the neurobiological underpinnings of ASD. This study investigated age- and sex-dependent behavioral and synaptic alterations following postnatal VPA administration during a critical developmental window (P30-P60). C57BL/6 female and male mice were exposed to a single intraperitoneal dose of VPA on postnatal day 14. Behavioral assessments included social interaction, open field, olfactory preference, and Morris water maze tests. Molecular analyses focused on the postsynaptic proteins Neurogranin (Nrgn) and PSD-95 (Dlg4) across the hippocampus, prefrontal cortex, and olfactory bulb. Postnatal VPA exposure produced age- and sex-dependent behavioral variability rather than uniform deficits. Males exhibited more pronounced modulation in locomotor and social parameters, whereas females showed relative resilience in spatial learning measures. In the hippocampus, VPA induced a significant increase in Nrgn mRNA and PSD-95 protein in 1-month-old males, suggesting temporally restricted synaptic remodeling during early maturation. These molecular alterations were region-specific and interaction-driven, with limited treatment effects observed in the prefrontal cortex and olfactory bulb. Importantly, protein levels were primarily influenced by age and sex rather than treatment alone, indicating tightly regulated developmental modulation rather than sustained synaptic loss. Collectively, these findings demonstrate that postnatal VPA exposure perturbs the temporal dynamics of synaptic maturation in a sex- and region-dependent manner, highlighting hippocampal vulnerability during adolescence. The results emphasize the importance of incorporating developmental stage and biological sex in mechanistic studies of ASD-related neuroplasticity.
A fully automated immunoassay for plasma kallikrein-8: Development and evaluation in mild cognitive impairment.
Gupta I, Miura M, Kimura A … +8 more , Tanaka S, Takeda S, Nakajima T, Hashimoto M, Iwata K, Segawa T, Sato T, Shiosaka S
Brain Res · 2026 Jun · PMID 41819517 · Publisher ↗
BACKGROUND: Early diagnosis of dementia is critical for timely treatment and management before the disease progresses to a severe stage. In this study, we aimed to evaluate plasma kallikrein-8 (KLK8) as a potential bioma...
BACKGROUND: Early diagnosis of dementia is critical for timely treatment and management before the disease progresses to a severe stage. In this study, we aimed to evaluate plasma kallikrein-8 (KLK8) as a potential biomarker for early diagnosis at the mild cognitive impairment (MCI) stage. METHODS: We developed a fully automated KLK8 immunoassay using the Automated Immunoassay System HISCL-5000 and assessed its analytical performance. Using this method, plasma levels of KLK8, along with other well-established biomarkers-neurofilament light chain (NfL), tau, tau phosphorylated at threonine 181 (p-tau181), and amyloid β (Aβ) 40 and 42-were measured in eighty participants enrolled at the Osaka Psychiatric Medical Center. The cohort included twenty-six controls, forty-one with MCI, and thirteen with dementia. RESULTS: The newly developed fully automated KLK8 immunoassay demonstrated strong analytical performance using 30 µL of plasma. In clinical evaluations, plasma KLK8 levels were significantly elevated in the MCI group compared to controls. Correlation analysis revealed that KLK8 significantly correlates with plasma levels of NfL and tau, both early neurodegeneration markers, as well as Aβ40. These findings suggest that KLK8 may serve as a predictive marker of early neurodegeneration at the MCI stage. CONCLUSION: Plasma KLK8 levels may therefore predict the early stage of dementia and represent a promising biomarker for disease prognosis.
Intense training abolishes the two temporal windows of cycloheximide-induced amnesia in rats.
Medina AC, Bello-Medina PC, Quirarte GL … +1 more , Prado-Alcalá RA
Brain Res · 2026 Jun · PMID 41812972 · Publisher ↗
Several studies have identified two distinct time windows during memory consolidation that are sensitive to protein synthesis inhibitors, whereas only a single window is observed following enhanced training. These findin...
Several studies have identified two distinct time windows during memory consolidation that are sensitive to protein synthesis inhibitors, whereas only a single window is observed following enhanced training. These findings suggest that one or two waves of protein synthesis may be required for long-term memory formation, depending on the strength of the training. However, further intensifying the learning stimulus may counteract the disruptive effects of protein synthesis inhibitors. To test this hypothesis, we trained rats in an inhibitory avoidance task using either moderate or intense footshock. Rats then received systemic injections of a protein synthesis inhibitor at -0.5 h before training, or at 1.0, 2.5, or 5.5 h after training. Following moderate training, amnesia was observed when the inhibitor was administered at -0.5 or 2.5 h, but not at 1.0 or 5.5 h. In contrast, after intense training, the inhibitor had no effect on memory consolidation at any of these intervals. Together, these results indicate that memory consolidation induced by intense training is resistant to disruption by protein synthesis inhibition.
Ferroptosis mechanisms in early brain injury after subarachnoid hemorrhage.
Du W, Chen J, Cheng G … +3 more , Yang Y, Shi Y, Wang Y
Brain Res · 2026 Jun · PMID 41802694 · Publisher ↗
Subarachnoid hemorrhage (SAH) refers to the rupture of intracranial blood vessels, leading to blood entering the subarachnoid space. It is primarily caused by the rupture of intracranial aneurysms and represents a severe...
Subarachnoid hemorrhage (SAH) refers to the rupture of intracranial blood vessels, leading to blood entering the subarachnoid space. It is primarily caused by the rupture of intracranial aneurysms and represents a severe acute cerebrovascular disease. Early brain injury (EBI) denotes the pathological changes occurring within 72 h after SAH, including increased intracranial pressure, reduced cerebral blood flow, blood-brain barrier disruption, brain edema, oxidative stress, and neuroinflammation. Ferroptosis is an iron-dependent form of programmed cell death (PCD), and its mechanisms can be summarized into three interrelated aspects: iron metabolism, lipid peroxidation metabolism, and glutathione and amino acid metabolism. Recent studies indicate that ferroptosis is associated with EBI and is significantly correlated with a poor prognosis. This article reviews the latest research progress on ferroptosis in early brain injury after subarachnoid hemorrhage and provides new insights for future research.
IGFBP7 protects against endothelial apoptosis and blood-brain barrier disruption following oxygen-glucose deprivation/reoxygenation.
Zhu Y, Cui T, Chen M … +3 more , Xu M, Sima X, Wang D
Brain Res · 2026 Jun · PMID 41802693 · Publisher ↗
BACKGROUND: The blood-brain barrier (BBB) is a critical interface maintained by cerebral microvascular endothelial cells, which rely on tight junction (TJ) proteins like ZO-1 and occludin to regulate permeability. Follow...
BACKGROUND: The blood-brain barrier (BBB) is a critical interface maintained by cerebral microvascular endothelial cells, which rely on tight junction (TJ) proteins like ZO-1 and occludin to regulate permeability. Following ischemic stroke, BBB disruption and subsequent cerebral edema are major contributors to poor clinical outcomes. Insulin-like growth factor-binding protein 7 (IGFBP7) is highly expressed in these endothelial cells and has been implicated in both BBB formation and vascular repair. However, its specific role in stroke-induced endothelial injury has remained inconclusive. METHODS AND RESULTS: In this study, we investigated the function of IGFBP7 in an in vitro model of oxygen-glucose deprivation and reoxygenation (OGD/R) using mouse microvascular endothelial (bEnd.3) cells. We manipulated IGFBP7 levels through overexpression and siRNA-mediated silencing. Our results show that OGD/R treatment significantly decreased IGFBP7 expression, which led to increased BBB permeability, degradation of tight junction proteins, and cellular apoptosis. Importantly, overexpressing IGFBP7 mitigated these effects, restoring the expression of ZO-1 and reducing apoptosis. Conversely, silencing IGFBP7 exacerbated both tight junction protein degradation and cell apoptosis. CONCLUSION: Endothelial IGFBP7 exerts a protective role in ischemic stroke by blunting OGD/R-mediated BBB damage and thus, it may represent an interesting novel therapeutic target to be explored in future clinical investigation.
Hormonal modulation after deep brain stimulation and spinal cord stimulation: a scoping review mapping evidence across targets and indications.
Buccilli B, Buccilli PE
Brain Res · 2026 Jun · PMID 41802692 · Publisher ↗
BACKGROUND: Deep brain stimulation (DBS) and spinal cord stimulation (SCS) are widely used neuromodulation therapies for movement disorders, pain, neuropsychiatric conditions, and other indications. Beyond symptom contro...
BACKGROUND: Deep brain stimulation (DBS) and spinal cord stimulation (SCS) are widely used neuromodulation therapies for movement disorders, pain, neuropsychiatric conditions, and other indications. Beyond symptom control, both techniques may modulate neuroendocrine and metabolic pathways, but the available evidence is fragmented across targets, indications, and hormone systems. This review aims to map the existing human and preclinical evidence on hormonal and neuroendocrine changes associated with DBS and SCS across different stimulation targets and clinical indications. METHODS: We conducted a scoping review following PRISMA guidelines. Experimental and clinical studies, case series, and case reports reporting hormonal, endocrine, or neuropeptide outcomes during or after DBS or SCS were eligible. Data were charted for study design, population (human/animal), indication, stimulation target/level, stimulation type, hormones assessed, direction of hormonal change, associations with clinical outcomes, and side effects. Given heterogeneity of designs and outcomes, results were synthesized narratively and organized by stimulation modality. RESULTS: Eighteen studies were included: thirteen focused on DBS and five on SCS. DBS of the subthalamic nucleus, hypothalamus, nucleus accumbens, bed nucleus of the stria terminalis, medial forebrain bundle, and basolateral amygdala was associated with changes in prolactin, TSH, ACTH, cortisol/corticosterone, testosterone, thyroid hormones, ghrelin, NPY, insulin, leptin, and oxytocin, with some studies linking these changes to weight gain, mood elevation, pain behavior, or OCD symptom trajectories. SCS studies reported modulation of leptin and catecholamines in humans, oxytocin release in analgesia models, and norepinephrine dynamics in cardiac and autonomic contexts. CONCLUSIONS: DBS and SCS can modulate multiple endocrine axes in a target- and indication-specific manner, but the literature is sparse, heterogeneous, and largely exploratory, especially for SCS. Systematic hormone monitoring in neuromodulation trials, with standardized reporting of endocrine outcomes, is needed to clarify mechanisms, predict responders, and anticipate metabolic and neuropsychiatric side effects.
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